Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 20, Issue 3, Pages 819-833Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E08-08-0798
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- NIGMS NIH HHS [GM-069957, R01 GM069957-05, R01 GM069957] Funding Source: Medline
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The S-phase DNA damage checkpoint slows the rate of DNA synthesis in response to damage during replication. In the fission yeast Schizosaccharomyces pombe, Cds1, the S-phase-specific checkpoint effector kinase, is required for checkpoint signaling and replication slowing; upon treatment with the alkylating agent methyl methane sulfonate, cds1 Delta mutants display a complete checkpoint defect. We have identified proteins downstream of Cds1 required for checkpoint-dependant slowing, including the structure-specific endonuclease Mus81 and the helicase Rqh1, which are implicated in replication fork stability and the negative regulation of recombination. Removing Rhp51, the Rad51 recombinase homologue, suppresses the slowing defect of rqh1 Delta mutants, but not that of mus81 Delta mutant, defining an epistatic pathway in which mus81 is epistatic to rhp51 and rhp51 is epistatic to rqh1. We propose that restraining recombination is required for the slowing of replication in response to DNA damage.
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